title: The clinical diversity and role of chemotherapy in lymphoproliferative disorder in liver transplant recipients.
abstract: OBJECTIVE
  Post-transplant lymphoproliferative disorder is a well-documented complication with an incidence ranging from 2 to 10%, depending on the organ transplanted. Yet despite our increased understanding of the pathophysiology of this disease and the various treatments available, the mortality remains high at 60-80%. We present the clinical and histological features of ten adult liver transplant recipients with post-transplant lymphoproliferative disorder presenting over a 15-year period and review the therapeutic options.
  
  
  METHODS
  CD20/CD45RO immunostaining was used for T/B-cell markers; polymerase chain reaction and in-situ hybridisation for Epstein-Barr virus genome detection; kappa/lambda immunostaining and gene rearrangement analysis for clonality.
  
  
  RESULTS
  There were six females and four males (age range 24-56) with onset of post-transplant lymphoproliferative disorder-symptoms ranging from 3 to 72 months post transplant. Sites of post-transplant lymphoproliferative disorder included liver (n=4), lymph nodes (n=5), bone marrow (n=2), lungs (n=2), kidneys (n=2), brain, ovaries,: and pancreas (n=1). All lesions were classified as high-grade lymphoma, of B-cell lineage (9 tested); Epstein-Barr virus genome was detected in 7/10 cases. Three tumours were monoclonal; four were polyclonal and three undetermined. Treatment included immunosuppression reduction, antiviral therapy with acyclovir and/or chemotherapy (CHOP or VAPEC-B). Survival times for those patients not treated with chemotherapy were from 9 days to 30 months, whereas those receiving chemotherapy had remission times of 4 to 48 months.
  
  
  CONCLUSIONS
  Longer-term remissions can be achieved in patients treated with systemic chemotherapy, although not without morbidity. Clonality assessment is important but treatment decisions should be based primarily on clinical features of progression, as polyclonal tumours can behave as aggressively as monoclonal tumours.
authors.affiliation: Institute of Liver Studies, King's College Hospital and King's College School of Medicine and Dentistry, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: McCarthy
authors.forename: J
authors.initials: J
authors.lastname: Ramage
authors.forename: A
authors.initials: A
authors.lastname: McNair
authors.forename: E
authors.initials: E
authors.lastname: Gane
authors.forename: B
authors.initials: B
authors.lastname: Portmann
authors.forename: A
authors.initials: A
authors.lastname: Pagliuca
authors.forename: M
authors.initials: M
authors.lastname: Rela
authors.forename: N
authors.initials: N
authors.lastname: Heaton
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D014412:Tumor Virus Infections / Q000188:drug therapy*; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone